JP2007537211A - Alkylated derivatives of p-menthan-3-ol and their use as cooling agents - Google Patents

Abstract

The present invention relates to a crystallized 3-alkylated (1R, 4S) -p-menthan-3-ol derivative of formula A or B, wherein when R ² represents hydrogen or a methyl group, R ¹ is — (CH ₂ ) Represents an n-OH group (the value of n may be 0, 1, 2 and 3), or when R ² represents a hydroxy group, R ¹ represents a methyl group or — (CH ₂ ) n— Represents an OH group (value of n may be 1, 2 and 3). The present invention also relates to a method for preparing the derivative and a perfume, cosmetic or food composition containing the derivative.

Description

  The present invention relates to novel crystallized p-menthan-3-ol alkylated derivatives and their application, in particular as refreshing agents.

  There is always a need for substances that provide a fresh effect in the oral cavity or on the skin. In the case of beverages, candy, foods including chewing gum, and dental, bodily or medicinal hygiene products, there is a particular need for substances that produce a particularly cool sensation without any other effect on aroma or flavor. A number of chemically well-defined substances with strong cooling power are known. The best known is l-menthol, the main component of some essential oils of mint (Mentha spp.), For example Mentha Arvensis, from which it is very much crystallized. It can be isolated in high purity. Menthol is used extensively in food and dental hygiene formulations because it is inexpensive regardless of whether it is derived from natural or synthetic products. However, in addition to too high volatility, l-menthol has several other disadvantages including bitterness in addition to the typical odor that clearly reminds mint, so these properties are not desirable in formulations where it is undesirable. l-Menthol is inappropriate. In addition, when used at high concentrations, a burning sensation can occur and often interacts with other components of the fragrance mixture.

  For these reasons, the synthesis of substances that are free of bitterness and odor and produce the most fresh and lasting physiological freshness possible has long been studied.

  It would also be desirable to obtain such materials in a crystallized state.

  The first solution involves increasing the molecular weight of menthol while retaining the basic structure. Hydroxylated menthol derivatives such as hydroxy-8-p-menthan-3-ol are described in US Pat. No. 5,959,161. Menthyl mono-succinate and its use as a refreshing agent is claimed in US Pat. Nos. 5,725,865 and 5,843,466. Similarly, the corresponding monoglutarate is described in WO2003 / 043431. Mixed carbonate esters of menthyl with polyols such as glycerol and propylene glycol, as described in US Pat. No. 3,419,543, are also good candidates. l-menthyl lactate is described in DE-A-2608226.

  Other solutions include grafting groups substituted with alkyl and hydroxyl groups onto menthol in order to obtain derivatives having a menthoxy group. Thus, many derivatives in this category have been shown to meet the aforementioned requirements. Among them, (−)-menthoxypropane-1,2-diol described in US Pat. No. 4,459,425 of Takasago Perfumery Co. can be mentioned. Menton cyclic acetals such as glycerol acetal described in US Pat. No. 5,266,592 relate to this category.

  Another category of cool products having a p-menthan-3-yl skeleton is grafting of carboxamide functional groups onto the ring. Of the many derivatives synthesized by Wilkinson Sword Ltd. and claimed in various patents, N-ethyl-p-menthane-3-carboxamide, known as WS-3, is still manufactured. Widely used. It has also been found that p-menthan-3-yl units are not essential and appropriately substituted N-alkylcarboxamides can be very active. This is the case for 2-isopropyl-N, 2,3-trimethylbutyramide, also known as WS-23.

  The Nestec company recently discovered certain pyrrolidinylfuranone derivatives, particularly 4-methyl-3- (1-pyrrolidinyl) -2 [5H] furanone in colored malt with a very strong cooling effect. The use of these materials as cooling agents is claimed in US Pat. No. 6,592,884. However, under normal conditions using products with a cooling effect, the use of these enamines is hampered by their relatively poor stability, accompanied by the generation of an unpleasant odor of pyrrolidine and significant browning.

  French Patent Application No. 2359604 describes the use of menthol derivatives having a 2-hydroxyethyl group on the 3-position carbon of the p-menthanyl unit as a novel refreshing substance. The 3-hydroxy-p-menthane-3-ethanol actually obtained by the method described in this document has the appearance of a syrupy liquid and is composed of at least two sets of stereoisomers, each approximately 85: A ratio of 15. It was subsequently observed that the method of obtaining this mixture was also responsible for the presence of several other accessory ingredients that changed the expected performance primarily due to the presence of perceptible menthol odor and bitterness. .

  Surprisingly, Applicants have discovered that a new crystallized 3-alkylated (1R, 4S) -p-menthan-3-ol derivative produces a strong and lasting physiological freshness without bitterness and odor I discovered that.

（上式において、Ｒ²が水素又はメチル基を表す場合、Ｒ¹は−（ＣＨ₂）ｎ−ＯＨ基（ｎの値は０、１、２及び３であってよい）を表し、あるいはＲ²がヒドロキシ基を表す場合、Ｒ¹はメチル基又は−（ＣＨ₂）ｎ−ＯＨ基（ｎの値は１、２及び３であってよい）を表す。） This is why the subject of this application is a crystallized 3-alkylated (1R, 4S) -p-menthan-3-ol derivative of formula A or B.

(In the above formula, when R ² represents hydrogen or a methyl group, R ¹ represents a — (CH ₂ ) n —OH group (the value of n may be 0, 1, 2, and 3), or R ^{When 2} represents a hydroxy group, R ¹ represents a methyl group or a — (CH ₂ ) n—OH group (the value of n may be 1, 2 and 3).

In preferred conditions for carrying out the invention, R ² is hydrogen or a methyl group. In other preferred conditions for practicing the present invention, R ² is a hydroxy group. In yet another preferred condition for practicing the present invention, the value of n is 0, 1 or 2, especially 0 or 1.

Among the compounds of the present invention, the following can be mentioned more specifically:
(−)-(1R, 3R, 4S) -3-hydroxy-p-menthane-3-ethanol “1a”
(−)-(1R, 3S, 4S) -3-hydroxy-p-menthane-3-ethanol “1b”
(−)-(1R, 3R, 4S) -3-hydroxy-p-menthane-3-methanol “2a”
(−)-(1R, 3S, 4S) -3-hydroxy-p-menthane-3-methanol “2b”

  The chemical formula of the identified compound is included at the end of the description.

The subject of the present application is also a crystallized 3-alkylated (1R) of formula A or B wherein R ² represents H and R ¹ represents a — (CH ₂ ) n—OH group (n = 1). , 4S) -p-menthan-3-ol derivatives, in order to obtain the intended 3-hydroxy-p-menthane-3-ethanol isomer with an alkyl α-halogenoacetate and a purity greater than 95% A Reformatzky reaction is carried out with (-)-menton, and then the β-hydroxyester thus obtained is reduced to 1,3-diol using a hydride such as LiAlH _4. To do.

The subject of this application is also the crystallized 3-alkylated (1R, 4S) of formula A above, wherein R ² represents H and R ¹ represents a — (CH ₂ ) n —OH group (n = 0). ) -P-Mentan-3-ol derivatives, which are isolated and optionally purified, for example by crystallization, in order to obtain the intended 1,2-diol. Such a vinyl magnesium halide is condensed with (−)-menton, and then the resulting tertiary vinyl carbinol is acetylated and subjected to an ozonolysis treatment to obtain an ozonide, and the ozonide is treated with sodium borohydride in particular. It is preferably characterized in that it is reduced in-situ and the acetate thus produced is hydrolyzed.

The subject of this application is also the crystallized 3-alkylated (1R, 4S) of formula B above, wherein R ² represents H and R ¹ represents a — (CH ₂ ) n—OH group (n = 0). ) -P-Mentan-3-ol derivatives in order to obtain the intended 1,2-diol isolated and optionally purified, for example by crystallization, The cyanohydrin is selectively prepared and then reduced with hydride.

The present application also, R ² represents a hydroxy group, and R ¹ is - (CH ₂₎ represents an n-OH group (n = 0), crystallized 3-alkylation of the above formula A (1R, 4S) -p-Mentan-3-ol derivatives, such as halogens such as vinylmagnesium bromide, to obtain the intended triol isolated and optionally purified, for example by crystallization. It is characterized in that vinylmagnesium fluoride is condensed with (−)-menton, then the resulting tertiary vinyl carbinol is epoxidized and then subjected to alkaline hydrolysis.

  The p-menthan-3-ol derivative which is the subject of the present invention has very useful properties and qualities. In particular, they produce a fresh feeling without the characteristic odor of menthol and without bitterness.

  These properties are a reason for using the above-mentioned p-menthan-3-ol derivatives in perfumes and cosmetics.

  It also pertains to the subject matter of the present application, in particular as a refreshing agent or for its menthol odor, a perfume or cosmetic composition or a food composition characterized in that it contains the above-mentioned p-menthan-3-ol derivative, That is why.

  These compositions may be, for example, solids or liquids and are in commonly used forms such as but not limited to lotions, aftershave lotions, lotions, deodorants, shampoos, shaving creams, toothpastes and other dental hygiene products, It may be ointments, aerosols, fragrances for foodstuffs (including but not limited to candy, chewing gum, ice cream, beverages), and tobacco. These are prepared by conventional methods.

  p-Mentan-3-ol derivatives can be incorporated into excipients commonly used in these compositions, such as gum arabic, lactose, starch, aqueous or non-aqueous vehicles, and preservatives.

  The subject of the present invention is also a method for preparing the above-mentioned composition, characterized in that the p-menthan-3-ol derivative is mixed with an acceptable component by a method known per se.

  The preferred conditions for using the above-mentioned p-menthan-3-ol derivative also apply to the other objects of the invention mentioned above, in particular perfumes or cosmetic compositions.

  The following examples illustrate this application.

  Examples 1 and 2: (−)-(1R, 3R, 4S) -3-hydroxy-p-menthane-3-ethanol “1a” and (−)-(1R, 3S, 4S) -3-hydroxy-p- Menthane-3-ethanol "1b": a solution of 0.1 mol of 85% pure (-)-menton and 0.16 mol of ethyl bromoacetate in 100 mL of tetrahydrofuran (THF) was previously activated with a small amount of iodine. Slowly add 0.3 mol of powdered zinc to a boiling and stirring suspension. As soon as the reaction starts, the heating is interrupted and the addition is performed so that the exothermic reaction maintains the reflux of the solvent. When addition is complete, heat again for 1 hour. The cooled reaction mixture is filtered over celite, then the celite is washed with 250 mL THF, then 250 mL ethyl acetate.

  The combined organic phases are subsequently washed with dilute hydrochloric acid solution and brine. The organic phase is dried and the solvent is distilled off. The residue is chromatographed on silica gel using hexane containing ethyl acetate in increasing proportion as elution solvent. The two Reformatzky diastereoisomer adducts are thus isolated in a ratio of 4: 1 (yield 70-75%).

  A 20% dry THF solution of each isolated hydroxy ester is added to a boiling 1.5 molar equivalent THF suspension of lithium aluminum hydride.

  After refluxing for 3 hours, the reaction medium is cooled and ethyl acetate and dilute hydrochloric acid are subsequently added. The organic phase is separated and the aqueous phase is extracted with ethyl ether. The combined organic phases are dried and the solvent is removed.

  The residue is chromatographed on a small silica gel column using a hexane-ethyl acetate 95: 5 mixture as the eluting solvent. A solidifying oil is obtained. The crude solid is then crystallized from 1.5-2 volumes of hexane to obtain each of the two diastereoisomeric diols, yields of 70-80%.

Analysis: (−)-(1R, 3R, 4S) -3-hydroxy-p-menthane-3-ethanol “1a” melting point 80 to 82 ° C .; [α] _D −16 °; NMR ¹ H δ 0.77 to 0 .98 (2H, m), 0.90 (3H, d, J = 6.5 Hz), 0.91 (6H, d, J = 6.7 Hz), 1.03 (1H, ddd, J = 12. 9, 3.5, 2.0 Hz), 1.27 to 1.59 (3H, m), 1.60 to 1.93 (3H, m), 2.12 to 2.36 (2H, m), 2.23 (2H), 3.70-3.83 (1H, m), 3.99 (1H, ddd, J = 14.5, 10.3, 4.1 Hz); NMR ¹³ C δ 17.6, 20.0, 22.1, 23.3, 25.2, 27.5, 34.6, 40.5, 45.9, 49.7, 58.6, 75.0; mass spectrum m / z 00 (M +), 185,155,137,115 ( 100%), 97,81,69,55; IR spectrum (Nujol) v (cm ^-1) 856,1072,3299,3378.

(−)-(1R, 3S, 4S) -3-hydroxy-p-menthane-3-ethanol “1b” melting point 84-86 ° C .; [α] _D -33.4 °; NMR ¹ H δ 0.80-1 .02 (1H, m), 0.85 (3H, d, J = 6.7 Hz), 0.90 (3H, d, J = 6.2 Hz), 0.98 (3H, d, J = 6. 7Hz), 1.1 (2H, m), 1.26 to 1.50 (1H, m), 1.57 to 1.80 (3H, m), 1.83 to 2.00 (1H, m) 2.04 to 2.26 (2H, m), 2.30 (2H, s), 3.72 to 3.85 (1H, m), 3.93 (1H, ddd, J = 13.9, 10.8, 3.1 Hz); NMR ¹³ C δ 19.6, 22.4, 24.1, 24.8, 24.9, 30.3, 32.6, 35.1, 47.1, 54. 1, 59.2, 77.1; Mass spectrum m / z 200 (M +), 185, 155, 149, 143, 137, 129, 121, 115 (100%), 97, 88, 81, 69, 55; IR spectrum (Nujol) v (Cm ⁻¹ ) 866, 871, 1157, 3308.

  These two diols have no strong bitter or menthol odor, and have a strong cooling effect.

  Example 3: (-)-(1R, 3R, 4S) -3-Hydroxy-p-menthane-3-methanol "2a": First, a vinylmagnesium bromide solution was prepared by removing 0.15 mol of shaved magnesium and 15% odor It is prepared using 0.13 mol of vinyl fluoride THF solution. This solution is added under nitrogen to 80 mL of a (-)-menton 0.1 molar THF solution at a temperature of -20 to -30 ° C. After stirring for 2 hours, the reaction mixture is brought to ambient temperature, followed by cooling to 0 ° C. and adding ammonium chloride solution. The aqueous phase is decanted and extracted twice with 100 mL of ethyl acetate. The combined organic phases are then added to ice-cold 0.1N hydrochloric acid solution, saturated sodium bicarbonate and then brine. After drying with sodium sulfate, the oily residue (16.3 g) obtained by removing the solvent is dissolved in 100 mL of acetic anhydride to which 2.5 g (0.03 mol) of sodium acetate has been added. The mixture is boiled for 5 hours with stirring. After cooling, pour the reaction mixture onto crushed ice. After standing for 2 hours at ambient temperature, the mixture is extracted twice with 250 ml of a hexane: ethyl acetate = 1: 1 mixture. The organic phase is then washed several times with water, then with saturated sodium bicarbonate solution and finally with brine. The oily residue obtained after drying and evaporation of the solvent is chromatographed on 200 g of silica gel (MN Kieselgel 60-Macherey & Nagel), eluting with a mixture of hexane: ethyl acetate = 4: 1. In this way 11.2 g (50% yield) of acetylated vinyl carbinol and 20% unchanged vinyl carbinol are collected. The acetylated derivative is dissolved in 80 mL of a mixture of methanol and dichloromethane, followed by ozonolysis at -70 ° C. Excess ozone is removed by bubbling nitrogen through the reaction mixture, and then the reaction mixture is treated with a solution of sodium borohydride in ethanol (1 molar equivalent). The temperature is raised to 20-25 ° C. and after 2 hours the reaction mixture is diluted in ice water and then extracted twice with 150 mL of dichloromethane. After evaporation of the solvent, the residue is dissolved in 100 mL of methanol, 10 mL of 40% aqueous potassium solution is added, and the mixture is heated in a water bath for 2 hours. Methanol is distilled off at low temperature under reduced pressure, then diluted in ice water and adjusted to pH 5 with acetic acid. The reaction mixture is extracted twice with 100 mL of dichloromethane. After removal of the solvent, the remaining crude product is cooled to −20 ° C. overnight and crystallized from 2 volumes of hexane. 6.3 g (73% yield) of the desired product “2a” are obtained.

Analysis: melting point 80 to 82 ° C .; [α] _D −6.7 °; NMR ¹ H δ 0.77 to 1.05 (2H, m), 0.90 (3H, d, J = 6.2 Hz), 0 .91 (6H, d, J = 7.0 Hz), 0.18 (1H, ddd, J = 6.6, 4.3, 2.3 Hz), 1.35 to 1.60 (2H, m), 1.61-1.84 (3H, m), 1.66 (2H, s), 2.08 (1H, dh, J = 2.3, 7.0 Hz), 3.43 (1H, d, J = 10.8 Hz), 3.73 (1H, d, J = 10.8 Hz); NMR ¹³ C δ 18.2, 20.5, 22.4, 23.6, 26.1, 27.8, 35. 1, 44.9, 47.4, 63.4, 75.0; mass spectrum m / z 186 (M +), 155 (100%), 137, 125, 111, 101, 95, 81, 74, 6 9, 55, 43; IR spectrum (Nujol) v (cm ⁻¹ ) 819, 906, 1042, 1165, 1265, 3219, 3526.

  Example 4: (−)-(1R, 3S, 4S) -3-hydroxy-p-menthane-3-methanol “2b”: boron trifluoride ether (7.8 mL, 58 mmol) and trimethylsilyl cyanide (7.2 mL) , 58 mmol) is added to 10 g (13 mL, 64 mmol) of (−)-menton. The mixture is stirred at ambient temperature for 1 hour and then at 60 ° C. for 30 minutes. The reaction is interrupted by adding 100 mL of a cooled 2N aqueous hydrochloric acid solution. The mixture is extracted with ether (3 times 100 mL) and the combined organic extracts are washed with 5% sodium bicarbonate solution and then with brine. After drying over sodium sulfate and evaporation of the solvent, the residue is chromatographed on a silica gel column and eluted with a mixture of hexane: ether = 9: 1. In this way, 4 g of the desired cyanohydrin (having a cyano group in the axial position) is isolated, and the yield is 38%.

  This cyanohydrin (3 g, 17 mmol) is dissolved in 75 mL of anhydrous toluene under nitrogen. While cooling to −40 ° C., diisobutylaluminum hydride (30 mL of 1.2 M toluene solution) is added over 1 hour. When the addition is complete, stir for 1 hour while maintaining this temperature. The reaction mixture is then poured into a stirred mixture of 40 mL of ice-cold saturated ammonium chloride solution (40 mL) and ether (40 mL). Then 60 mL of 5% aqueous sulfuric acid is added and the mixture is stirred vigorously at ambient temperature for 2 hours. The reaction mixture is extracted with ether (twice, 100 mL) and the combined organic phases are concentrated under reduced pressure. The residue is dissolved in 50 mL of methanol and treated with sodium borohydride (20 mmol, 0.76 g) at ambient temperature. 2.1 g of crude product is obtained by conventional methods and then purified by chromatography on a silica gel column eluting with a hexane: ethyl acetate = 4: 1 mixture and then with a 1: 1 mixture. This gives 1.9 g of pure diol “2b”.

Analysis: melting point 48-50 ° C .; [α] _D −19.6 °; NMR ¹ H δ 0.73—1.02 (2H, m), 0.79 (3H, d, J = 7.0 Hz), 0 .91 (3H, d, J = 7.0 Hz), 0.97 (3H, d, J = 7.0 Hz), 1.1 (1H, dq, J = 13.1, 3.1 Hz), 1. 23-1.36 (1H, m), 1.38-1.58 (1H, m), 1.64 (1H, ddd, J = 10.1, 6.6, 3.1 Hz), 1.70 ˜1.81 (1H, m), 2.04 to 2.24 (2H, m), 3.15 (2H, bs), 3.63 (1H, d, J = 11.2 Hz), 3.69 (1H, d, J = 11.2 Hz); NMR ¹³ C δ 19.5, 22.4, 23.6, 24.7, 30.1, 35.0, 44.9, 52.0, 62.9 , 76.4; EI-MS / Z 186 (M +), 169,155,137,111,101,95,83,81,69,59,55,43,41.

  Example 5: (1R, 3R, 4S) -3-hydroxy-p-menthane-3- (ethane-1,2-diol) “3”: 3-chloroperbenzoic acid (70% suspension in water, 1. 1 molar equivalent) is added in portions to 100 mL of a solution of the previous vinyl carbinol (0.1 mol) in dichloromethane with stirring at 0 ° C. After 10 hours, the precipitate of 3-chlorobenzoic acid is filtered with a Buchner. Wash the filtrate with saturated sodium bicarbonate solution. After purification by silica gel column chromatography, an oily epoxy carbinol was obtained in 80% yield, then dissolved in 70 mL of THF, then 0.5 molar equivalent of lithium hydroxide dissolved in a minimum amount of water was added, The mixture is stirred at 50 ° C. for 2 hours. The volume of the reaction mixture is reduced by evaporation of the solvent under reduced pressure and separated in a mixture of water and ether. The organic phase is washed with dilute hydrochloric acid solution and then with brine. After removal of the solvent, purification by elution with a hexane: ethyl acetate = 1: 1 mixture by chromatography on a silica gel column, the expected triol “3” is isolated in 60% yield.

Analysis: mp 34-36 ° C .; [α] _D -14.6 °; NMR ¹ H δ 0.70-1.10 (4H, m), 0.80 (3H, d, J = 6.6 Hz), 0 .91 (3H, d, J = 6.6 Hz), 0.92 (3H, d, J = 6.6 Hz), 1.2 to 1.9 (8H, m), 3.29 (1H, dd, J = 6.6, 4.25 Hz), 3.71 (1H, dd, J = 12.0, 7.0 Hz), 3.88 (1H, m); NMR ¹³ C δ 18.4, 21.9, 23.1, 23.9, 25.7, 30.5, 33.6, 38.3, 45.9, 61.0, 61.2, 65.7; mass spectrum m / z 198, 183 (100 %), 167, 155, 149, 139, 125, 119, 111, 105, 95, 81, 67, 55; IR spectrum (Nujol) v (cm ⁻¹ ) 8 96, 984, 1032, 1065, 3382.

  The refreshing effect of this compound, which can exist in the form of the two isomers “3a” and “3b”, is strong and its bitter taste is virtually unperceivable. Due to the hydrophilic nature of this compound, it can be used in applications where this property is required.

  Specific rotation was measured at a concentration of 1% (mass / volume) in chloroform, and NMR spectra were recorded on a spectrometer operating at 250 MHz using chloroform as a solvent unless otherwise indicated.

  Comparative Example: A compound similar to the present invention was also prepared.

  When the synthesis method of Example 1 is applied to l-isomentone, d-mentholone or d-isomentone, three sets of diols are (1S, 3R, 4S) and (1S, 3S, 4S), (1S, 3R, 4R) And (1S, 3S, 4R), (1R, 3R, 4R) and (1R, 3S, 4R). All these diols have a cooling effect, but are incomparable to those prepared from l-menton.

  The strength of the cooling effect of diols “4”, “5” and “6” shown below is reduced, has a perceivable bitter taste, and is even worse with compound “4”. The same disadvantages are observed in the case of 1,4-diol “7” and 1,5-diol “8” shown later. Introducing the methoxymethyl group into the (1R, 3R, 4S) -3-hydroxy-p-menthane-3-ethanol structure as in the case of the isomeric diols “9a” and “9b” shown below Among them, it has the effect of increasing both refreshing feeling and bitterness.

  Neither of the two isomers of the triol “10” produces an intense refreshing feeling comparable to the diol “1”, “2” or “3”.

  Of (1R, 3R, 4S) -3-hydroxy-p-menthane-3-methanol and (1R, 3R, 4S) -3-hydroxy-p-menthane-3-ethanol, as in the case of diol “11” O-alkylated derivatives do not have a particularly strong cooling effect, but their bitter taste is very pronounced.

  (1R, 3R, 4S) -3-hydroxy-p-menthane-3-methanol or (1R, 3R, 4S) -3-hydroxy-p-menthane, such as acetate “12” and mono-succinate “13” Esterification of only one primary alcohol functional group of -3-ethanol results in a compound with unexpected quality. Mixed carbonate “14” of l-menthol and (1R, 3R, 4S) -3-hydroxy-p-menthane-3-methanol, or (1R, 3R, 4S) -3-hydroxy-p-menthane-3 The same applies to the mixed carbonate ester “15” with ethanol.

Composition Examples Example 1: (1) Fragrance composition for aftershave lotion:

  (2) Use of this composition in the preparation of after-shave lotion: This composition is used in the lotion of the following composition approximately 0.5-1%.

  Example 2: (1) Fragrance composition for shaving cream:

  (2) Use of this fragrance composition in the preparation of a shaving cream: The fragrance composition is used in an amount of about 0.5 to 1% in a shaving cream having the following composition.

  Example 3: Fragrance for aerosol body deodorant:

  This perfume composition was used in the following aerosol composition.

  The container is filled with 70% of the previous mixture and 30% with an aerosol propellant (propane / butane mixture) of 2.5 bar.

  Example 4: Fragrance composition for oral cleanser: Approximately 0.2 g of (-)-(1R, 3R, 4S) -3-hydroxy-p-menthane-3-methanol is used per liter of the prepared oral cleanser. A refreshing effect is obtained.

  Example 5: Perfume composition for toothpaste: (-)-(1R, 3R, 4S) -3-hydroxy-p-menthane-3-methanol is used at approximately 0.05-2% by weight of the final product. In a preferred embodiment, it is envisaged to add approximately 0.1 to 0.15% by weight sodium saccharinate as a sweetener to eliminate the slight bitterness that this composition would have.

  Example 6: Fragrance composition for tobacco: Approximately 0.05 g of (−)-(1R, 3R, 4S) -3-hydroxy-p-menthane-3-ethanol is used per 1 kg of tobacco. A refreshing effect is obtained.

  Example 7: Perfume composition for boiled sweet: Prepare an aqueous solution (110 g of water) of sucrose (350 g) boiled at 107 ° C. Add 150 g of glucose syrup and boil at 148 ° C. Fragrance, citric acid and colorant are added at approximately 120 ° C. and 0.2 g of (−)-(1R, 3R, 4S) -3-hydroxy-p-menthane-3-methanol is added per kg of final product. A very clear cooling effect is obtained.

  Example 8: Fragrance composition of chewing gum: (-)-(1R, 3R, 4S) -3-hydroxy-p-menthane-3-methanol was added to a chewing gum paste prepared according to a conventional method in an amount of 0.2 to 1 Add 0.8 g.

Claims (11)

Crystallized 3-alkylated (1R, 4S) -p-menthan-3-ol derivative of formula A or B.

(In the above formula, when R ² represents hydrogen or a methyl group, R ¹ represents a — (CH ₂ ) n —OH group (the value of n may be 0, 1, 2, and 3), or R ^{When 2} represents a hydroxy group, R ¹ represents a methyl group or a — (CH ₂ ) n—OH group (the value of n may be 1, 2 and 3). ^2. Derivative according to claim 1, characterized in that R2 represents hydrogen or a methyl group. The derivative according to claim 1, wherein R ² represents a hydroxy group.   2. Derivative according to claim 1, characterized in that the value of n is 0 or 1. (−)-(1R, 3R, 4S) -3-hydroxy-p-menthane-3-ethanol,
(−)-(1R, 3S, 4S) -3-hydroxy-p-menthane-3-ethanol,
(−)-(1R, 3R, 4S) -3-hydroxy-p-menthane-3-methanol,
2. Derivative according to claim 1, selected from (-)-(1R, 3S, 4S) -3-hydroxy-p-menthane-3-methanol. The crystallized 3-alkylated (1R, 4S of formula A or B according to claim 1, wherein R ² represents H and R ¹ represents a-(CH ₂ ) n-OH group (n = 1). In order to obtain the intended 3-hydroxy-p-menthane-3-ethanol isomer, which is a process for the preparation of -p-menthan-3-ol derivatives, optionally isolated, alkyl alpha-halogenoacetates And a (-)-menton having a purity of more than 95%, a Reformatzky reaction is performed, and then the β-hydroxy ester thus obtained is reduced to 1,3-diol using a hydride. And how to. R ² represents H, and R ¹ is - (CH ₂₎ represents an n-OH group (n = 0), crystallized 3-alkylation of formula A according to claim 1 (1R, 4S) - In order to obtain the intended 1,2-diol, which is a process for the preparation of p-menthan-3-ol derivatives, which is isolated and optionally purified, the vinylmagnesium halide is combined with (−)-menthone. A method characterized by condensing, then acetylating the resulting tertiary vinyl carbinol, subjecting to ozonolysis to obtain an ozonide, reducing the ozonide, and hydrolyzing the acetate thus formed. . The crystallized 3-alkylated (1R, 4S)-of formula B according to claim 1, wherein R ² represents H and R ¹ represents a-(CH ₂ ) n-OH group (n = 0). In order to obtain the intended derivative, which is a process for the preparation of the p-menthan-3-ol derivative, which is isolated and optionally purified, the cyanohydrin of (−)-menton is selectively prepared, The method is characterized in that reduction is carried out using a hydride. The crystallized 3-alkylated (1R, 4S) of formula A according to claim 1, wherein R ² represents a hydroxy group and R ¹ represents a-(CH ₂ ) n-OH group (n = 0). A process for the preparation of a -p-menthan-3-ol derivative, wherein the magnesium magnesium halide is condensed with (-)-menton in order to obtain the intended derivative, which is isolated and optionally purified, Next, the tertiary vinyl carbinol obtained is epoxidized and then subjected to alkali hydrolysis.   A perfume or cosmetic composition comprising the p-menthan-3-ol derivative according to any one of claims 1 to 5.   A food composition comprising the p-menthan-3-ol derivative according to any one of claims 1 to 5.